Erectile impotence afflicts between ten and twenty million men in the United States. Basic physiologic data relating penile erection to the mechanisms controlling smooth muscle tone within the corpora cavernosa has been lacking. This poor understanding has restricted therapy for the organically impotent patient largely to surgical treatment by prosthetic devices. In particular, pharmacologic therapy for erectile dysfunction requires more complete understanding. It is the objective of this proposal to adapt in vitro methodology established for the study of smooth muscle physiology in other vascular tissue, for use in the investigation of human corpus cavernosum tissue. The overall aim is to gain a more complete understanding of physiologic mechanisms regulating both the relaxation of human corpus cavernosum tissue (erection) and the contraction of human corpus cavernosum tissue (flaccidity). In particular, the study will investigate 1) the prejunctional neuromodulation of adrenergic, cholinergic and the putative VIP containing nerves, 2) the role of VIP as the possible inhibitory (relaxation) neurotransmitter in human corpus cavernosum smooth muscle, 3) the role of the endothelium lining the lacunar space as a necessary mediator in the relaxation response to acetylcholine and other relaxant substances of corporal smooth muscle and 4) the cellular mechanisms by which relaxation is mediated in the smooth muscle cell of the the corpus cavernosum, specifically which cyclic nucleotides are associated with the relaxation induced by both electrical stimulation of nerve terminals and exogenous substances. It is anticipated that the knowledge gained from complete understanding of the mechanisms governing tone of the human corpus cavernosum smooth muscle will result in improved therapy, in particular pharmacologic therapy, for impotence and priapism.